A cornea is a transparent membrane with a thickness of about 0.5 mm, and has a five-layer structure which consists of corneal epithelial cells, a Bowman membrane, corneal stroma, a Descemet's membrane and corneal endothelial cells, in this order from the surface of body. Among these, although the corneal epithelial cells have high regenerating capability, a serious corneal ulcer might occur, or a nonreversible corneal opacity might be left, in the case where a disorder of the epithelial cells is serious. Therefore, there have been strong demands for measuring the degree of the disorder of the corneal epithelium quantitatively and carrying out a proper treatment in an earlier stage.
Since the conventional method for measuring the degree of a disorder of the cornea mainly depends on a visual inspection method, it is difficult to quantitate the disorder of the corneal epithelium, and there has been a demand for a method for representing the degree of the disorder of the cornea by a numeric value and for quantitating the degree of the disorder thereof.
In recent years, it has been known that by measuring a corneal transepithelial electric resistance (TER) that represents a barrier function of the cornea, the degree of the disorder of the cornea can be quantitatively measured (see Non-Patent Documents 1 to 3). The TER is indicated by the product of a corneal electric resistance value (Rc) and an area (a) of a portion to be measured, that is, TER=Rc×a. When the corneal epithelium has a disorder, the barrier function of the cornea is lowered to cause a low corneal TER value. The present inventors at first carried out experiments in which a cut-out cornea was fixed on a Ussing chamber by which an accurate TER can be determined by using a short-circuit current method, with the value of the area (a) being constant; however, since the cut-out cornea is different in its state from that in a living body, the experiments failed to reflect a true biological reaction. Therefore, the present inventors have found a method in which electrode needles are placed on the corneal epithelium and in the anterior chamber of a living eye and an electric resistance is measured by flowing an electric current therebetween (see Non-Patent Document 4). In this case, the measurement of TER is performed for a living cornea by using the principle of the Ussing chamber, and an accurate TER can be determined when the value of the measurement area (a) is constant.
However, since this method is an invasive method that is accompanied by an anterior chamber centesis, it is not possible to apply this method to human, and this method is not suitable for diagnosis and treatment of a corneal disorder in the clinical field.
Non-Patent Document 5 has disclosed a method for measuring a corneal resistance value about a living eye by using corneal contact lens (CL) provided with electrodes. Since this method is not invasive to respective portions of the eye, it may be applicable to human.
However, in this method, since a suitable insulator is not provided, a reliable electric current flow through the corneal epithelium cannot be made because of the existence of a lacrimal fluid on a surface of the eye, and the resulting measured value is considered to mainly represent the state of the lacrimal fluid rather than the state of the corneal epithelium. Moreover, since the CL is fixed onto the cornea by suction, the measuring device itself might cause a corneal disorder. Furthermore, it has been reported in the Japanese Society for Ocular Pharmacology in 2007 that this method failed to detect the existence of small corneal erosion. It can be considered that the electrodes fail to sufficiently detect the corneal disorder, since an electric current to be measured does not completely pass through the corneal epithelium. In addition, since this method does not take the area (a) through which the electric current flows into consideration, a TER that enables accurate evaluation of the corneal disorder cannot be determined. In this manner, the method of Non-Patent document 5 has a problem with the detection sensitivity.
Moreover, Patent Document 1 has disclosed a device for detecting a damage and the like of the corneal epithelium, and this device measures a reduction in a potential difference between a cornea and a sclera as an index for the damage. A corneal electric potential (Vc) serving as a parameter in Patent Document 1 is defined by the corneal electric resistance value (Rc) and an ion transporting function (current) (Ic) by the corneal endothelium, which is represented by Vc=Rc×Ic. Moreover, a corneal electric potential (Vc) is compared with the scleral electric potential (Vs) and k in Vc=kVs serves as an index indicating the corneal disorder. Consequently, k=Rc×Ic/Vs represents the corneal disorder. In this measurement, in order to reflect the Rc to the k, the Ic and the Vs need to be measured with high precision; however, in an actual operation, the current Ic generated from the corneal endothelium is very weak and is not constant. Since the scleral electric potential Vs varies depending on measuring conditions and individuals, it is not possible to determine a corneal disorder accurately when compared with this. Moreover, as described earlier, the TER, which directly reflects the corneal disorder, is represented by TER=Rc×a, and in order to determine a TER, the area (a) through which a current passes needs to be determined; however, it is not accurately determined by this measurement. Consequently, it is not possible to accurately measure the corneal disorder by using this measuring method.
Although Patent Document 1 roughly observes the electrophysiological phenomenon that the electric resistance value is lowered upon occurrence of a corneal disorder, its measuring principle and accuracy are far behind the technique of the present application.    patent document 1: JP-Y-S48-10716    non-patent document 1: Rojanasakul Y. et al., Int. J. Pharm., (66) 131-142 (1990)    non-patent document 2: Rojanasakul Y. et al., Int. J. Pharm., (63)1-16 (1990)    non-patent document 3: Chetoni P. et al., Toxicol In Vitro, (17)497-504 (2003)    non-patent document 4: Uematsu M. et al., Ophthalmic Research, 39, 308-314, 2007    non-patent document 5: Masamichi Fukuda et al., Atarashii Ganka (New Ophthalmology) 24(4):521-525, 2007